The goal of this project is to investigate the mechanisms of butorphanol-tratrate (STADOL)-induced pharmacological responses and to determine how tolerance to and physical dependence upon butorphanol develops. Butorphanol is classified as an agonist- antagonist narcotic analgesic which is stronger than morphine. Yet, butorphanol is exempted form control status. The studies reported in the literature have been conducted mainly following acute administration. The effects of continuous administration of butorphanol and its possible consequences (i.e., tolerance/ dependence) have not been adequately studies. Therefore, this project is designed to provide an animal model to systematically assess how butorphanol produces pharmacological responses and how butorphanol induces tolerance/dependence upon continuous administration. The evidence available at present is strongest for the involvement of different opioid receptors in the action of butorphanol. The following specific aims are designed to test the hypotheses formulated based on the rationale available. Four specific aims are proposed. They are: Aim I. Studies of the effects of acute butorphanol administration and their relationship to different opioid receptors. Aim II. Characterization of development of butorphanol using the model of continuous intracerebroventriculat (ICV) infusion of butorphanol via Osmotic Mini-pumps. Aim III. Characterization of development of butorphanol dependence. Aim IV. Characterization of the antagonistic properties of butorphanol in morphine dependent animals. The proposed systematic studies should (1) reveal the mechanism(s) of action of butorphamol, (2) provide awareness of the abuse liability of butorphanol, (3) suggest certain precautions to be considered during usage of butorphanol, (4) provide more rationale for the treatment of butorphanol abuse, and (5) identify the role(s) of different opioid receptors in the development of tolerance to and dependence on butorphanol.